Predicting future response to certolizumab pegol in rheumatoid arthritis patients: features at 12 weeks associated with low disease activity at 1 year

Objective

To determine the prognostic significance of data collected early after starting certolizumab pegol (CZP) to predict low disease activity (LDA) at week 52.

Methods

Data from 703 CZP‐treated patients in the Rheumatoid Arthritis Prevention of Structural Damage 1 (RAPID 1) trial through week 12 were used as variables to predict LDA (Disease Activity Score in 28 joints–erythrocyte sedimentation rate ≤3.2) at week 52. We identified variables, developed prediction models using classification trees, and tested performance using training and testing data sets. Additional prediction models were constructed using the Clinical Disease Activity Index (CDAI) and an alternate outcome definition (composite of LDA or American College of Rheumatology criteria for 50% improvement [ACR50]).

Results

Using week 6 and 12 data and across several different prediction models, response (LDA) and nonresponse at 1 year were predicted with relatively high accuracy (70–90%) for most patients. The best performing model predicting nonresponse by 12 weeks was 90% accurate and applied to 46% of the population. Model accuracy for predicted responders (30% of the RAPID 1 population) was 74%. The area under the receiver operating curve was 0.76. Depending on the desired certainty of prediction at 12 weeks, ～12–25% of patients required >12 weeks of treatment to be accurately classified. CDAI‐based models and those evaluating the composite outcome (LDA or ACR50) achieved comparable accuracy.

Conclusion

We could accurately predict within 12 weeks of starting CZP whether most established rheumatoid arthritis (RA) patients with high baseline disease activity would likely achieve/not achieve LDA at 1 year. Decision trees may be useful to guide prospective management for RA patients treated with CZP and other biologics.     

Role of tumour necrosis factor gene polymorphisms (-308 and -238) in breast cancer susceptibility and severity

Introduction  

Genetic polymorphisms in the promoter region of the tumour necrosis factor (TNF) gene can regulate gene expression and have been associated with inflammatory and malignant conditions. We have investigated two polymorphisms in the promoter of the TNF gene (-308 G>A and -238 G>A) for their role in breast cancer susceptibility and severity by means of an allelic association study.     

Volumetric rendering techniques: applications for three-dimensional imaging of the hip

Volumetric rendering is a new approach to three-dimensional (3D) imaging that overcomes many of the drawbacks of currently available surface-rendering systems. Its application on the Pixar Imaging System in two cases of acetabular fracture was assessed to illustrate the features of the technique. The fast-computing architecture and large memory of this system allow rapid generation of a series of high-quality 3D images in each plane of rotation (x or spinal axis, z or somersaulting axis) that can be viewed as independent static images or as an animated real-time video loop. Editing to remove the normal contralateral hemipelvis enhances appreciation of acetabular abnormalities. Every pixel of computed tomographic data is preserved, allowing representation of both soft tissue and bone as translucent overlap. The presentation of data also allows detection of subtle abnormalities and features and minimizes the artifact generation common in surface-rendered images.     

The decision-making process of genetically at-risk couples considering preimplantation genetic diagnosis: initial findings from a grounded theory study

Exponential growth in genomics has led to public and private initiatives worldwide that have dramatically increased the number of procreative couples who are aware of their ability to transmit genetic disorders to their future children. Understanding how couples process the meaning of being genetically at-risk for their procreative life lags far behind the advances in genomic and reproductive sciences. Moreover, society, policy makers, and clinicians are not aware of the experiences and nuances involved when modern couples are faced with using Preimplantation Genetic Diagnosis (PGD). The purpose of this study was to discover the decision-making process of genetically at-risk couples as they decide whether to use PGD to prevent the transmission of known single-gene or sex-linked genetic disorders to their children. A qualitative, grounded theory design guided the study in which 22 couples (44 individual partners) from the USA, who were actively considering PGD, participated. Couples were recruited from June 2009 to May 2010 from the Internet and from a large PGD center and a patient newsletter. In-depth semi-structured interviews were completed with each individual partner within the couple dyad, separate from their respective partner. We discovered that couples move through four phases (Identify, Contemplate, Resolve, Engage) of a complex, dynamic, and iterative decision-making process where multiple, sequential decisions are made. In the Identify phase, couples acknowledge the meaning of their at-risk status. Parenthood and reproductive options are explored in the Contemplate phase, where 41% of couples remained for up to 36 months before moving into the Resolve phase. In Resolve, one of three decisions about PGD use is reached, including: Accepting, Declining, or Oscillating. Actualizing decisions occur in the Engage phase. Awareness of the decision-making process among genetically at-risk couples provides foundational work for understanding critical processes and aids in identifying important gaps for intervention and future research.     

Health economics: implications for novel antirheumatic therapies

This paper discusses the pharmacoeconomics issues relating to the use of the newer therapies for rheumatoid arthritis (RA), namely the tumour necrosis factor (TNF) inhibitors. RESULTS: of recent studies have provided some evidence regarding the cost effectiveness of these agents. However, as the use of TNF inhibitors evolves--including their use in other systemic inflammatory diseases--this will be influenced by several factors including treatment of patients with early RA, longer term treatment, problems related to toxicity, quality of life, productivity, and market forces. Thus, pharmacoeconomic considerations are likely to remain a central factor in the use of novel therapies in rheumatology, and awareness about these will aid clinicians to select the most favourable therapies for their patients with arthritis.